A continuing long-range goal of the program is to examine the pathophysiology of renal disease by the use of clearance, micropuncture and biochemical techniques. Studies are being continued in an effort to clarify the functional characteristics of the chronically diseased kidney and in particular, to define the changes in the operation of control systems which accompany the evolution of uremia. Particular interest is devoted to the patterns of adaptation that occur in the residual nephrons as renal mass decreases with respect to the excretion of Na, PO4 and K. Studies on the peripheral metabolism of parathyroid hormone and in particular the role of the kidney are being extended with emphasis on the factors that control the degradation of the hormone. Studies are being continued on the pathogenesis and prevention of secondary hyperparathyroidism in chronic renal disease. Evidence in experimental animals indicates that the development of hyperparathyroidism may be prevented by dietary manipulations. These studies are extended to include long-term follow-up of patients with renal disease. Muscle metabolism of uremic animals is being studied. The effects of insulin and parathyroid hormone on amino acid release from muscle are being explored in normal and uremic animals. Glomerular permeability measurements using experimental models are being performed. The effect of therapeutic agents on the natural history of experimental and spontaneously occurring glomerulonephritis is being studied. Studies on the biochemical adaptations occurring in the diseased kidney are being continued with emphasis on the mechanisms that regulate acid excretion, gluconeogenesis and substrate oxidation. The functional patterns and mechanisms responsible for post-obstructive diuresis are being investigated using animal models. Maturation of tubular function in the fetal, neonatal and mature kidney is studied. A second general area of interest relates to the biology of ion transport across isolated membranes (toad bladder and frog skin). BIBLIOGRAPHIC REFERENCES: Wiesmann, W.P., Sinha, S., and Klahr, S. Effects of ionophore A21387 on baseline and vasopressin-stimulated sodium transport in the toad bladder. J. Clin. Invest. 59: 418, 1977. Wiesmann, W.P., Sinha, S., and Klahr, S. Effects of insulin, ADH and cyclic AMP on sodium transport in the toad bladder. Am. J. Physiol. 232: F307, 1977.